Skip to main content

Advertisement

SpringerLink
Log in

Paraneoplastic Syndromes in Thymoma: An Immunological Perspective

  • Thymoma
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

T lymphocyte development occurs primarily during fetal life through cell-to-cell interactions with epithelial and dendritic cells. Evidence now supports the concept that thymic function continues during adulthood, which may explain why thymic neoplasms are associated with immunodeficiency and autoimmune illness. A broad variety of autoimmune conditions are observed in patients with thymic tumors, especially hematological and paraneurological syndromes, including aplastic anemia, pure red cell aplasia and myasthenia gravies, encephalomyelitis, cerebellar degeneration, sensory neuropathies, and Lambert-Eaton myasthenic syndrome. A more thorough understanding of the immunological dysfunction in patients with thymoma and thymic carcinoma promises to contribute to the overall understanding of human immunology and improve the clinical management of patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Good RA, Gabrielsen AE. The Function of the Thymus. Med Sci. Jan 1964;15:54–61.

    PubMed  CAS  Google Scholar 

  2. Goldrath AW, Bevan MJ. Selecting and maintaining a diverse T-cell repertoire. Nature. 1999;402(6759):255–262. doi:10.1038/46218

    Article  PubMed  CAS  Google Scholar 

  3. Al-Harthi L, Marchetti G, Steffens CM, Poulin J, Sekaly R, Landay A. Detection of T cell receptor circles (TRECs) as biomarkers for de novo T cell synthesis using a quantitative polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA). J Immunol Methods. 2000;237(1–2):187–197. doi:10.1016/S0022-1759(00)00136-8

    Article  PubMed  CAS  Google Scholar 

  4. Weber G, Stigliani R. Pathology of tumors of the parenchyma of the thymus. Arch De Vecchi Anat Patol. 1950;15(1):25–122.

    PubMed  CAS  Google Scholar 

  5. Fink R. Diagnosis of tumors of the thymus. Schweiz Med Wochenschr. 1950;80(34):892–894.

    PubMed  CAS  Google Scholar 

  6. van der Geld HW, Strauss AJ (1966) Myasthenia gravis Immunological relationship between striated muscle and thymus. Lancet. 1(7428):57–60. doi:10.1016/S0140-6736(66)92356-7

    PubMed  Google Scholar 

  7. Parry EH, Kilpatrick GS, Hardisty RM. Red-cell aplasia and benign thymoma; studies on a case responding to prednisone. Br Med J. 1959;46(5130):1154–1156.

    Article  Google Scholar 

  8. Oosterhuis HJ, Bethlem J, Feltkamp TE. Muscle pathology, thymoma, and immunological abnormalities in patients with myasthenia gravis. J Neurol Neurosurg Psychiatry. 1968;31(5):460–463.

    Article  PubMed  CAS  Google Scholar 

  9. Jacobs EM, Hutter RV, Pool JL, Ley AB. Benign thymoma and selective erythroid aplasia of the bone marrow. Cancer. 1959;12(1):47–57. doi:10.1002/1097-0142(195901/02)12:1<47::AID-CNCR2820120110>3.0.CO;2-Q

    Article  PubMed  CAS  Google Scholar 

  10. Good RA, Maclean LD, Varco RL, Zak SJ. Thymic tumor and acquired agammaglobulinemia: a clinical and experimental study of the immune response. Surgery. 1956;40(6):1010–1017.

    PubMed  CAS  Google Scholar 

  11. Gafni J, Michaeli D, Heller H. Idiopathic acquired agammaglobulinemia associated with thymoma. Report of two cases and review of the literature. N Engl J Med. 1960;263:536–541.

    Article  PubMed  CAS  Google Scholar 

  12. Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003;105(4):546–551. doi:10.1002/ijc.11099

    Article  PubMed  CAS  Google Scholar 

  13. Hoffacker V, Schultz A, Tiesinga JJ, et al. Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood. 2000;96(12):3872–3879.

    PubMed  CAS  Google Scholar 

  14. Masci AM, Palmieri G, Vitiello L, et al. Clonal expansion of CD8+ BV8 T lymphocytes in bone marrow characterizes thymoma-associated B lymphopenia. Blood. 2003;101(8):3106–3108. doi:10.1182/blood-2002-08-2638

    Article  PubMed  CAS  Google Scholar 

  15. Montella L, Masci AM, Merkabaoui G, et al. B-cell lymphopenia and hypogammaglobulinemia in thymoma patients. Ann Hematol. 2003;82(6):343–347. doi:10.1007/s00277-003-0635-z

    Article  PubMed  CAS  Google Scholar 

  16. Strobel P, Rosenwald A, Beyersdorf N, et al. Selective loss of regulatory T cells in thymomas. Ann Neurol. 2004;56(6):901–904. doi:10.1002/ana.20340

    Article  PubMed  CAS  Google Scholar 

  17. Tarr PE, Sneller MC, Mechanic LJ, et al. Infections in patients with immunodeficiency with thymoma (Good syndrome) Report of 5 cases and review of the literature. Medicine (Baltimore). 2001;80(2):123–133. doi:10.1097/00005792-200103000-00005

    Article  CAS  Google Scholar 

  18. Tormoehlen LM, Pascuzzi RM. Thymoma, myasthenia gravis, and other paraneoplastic syndromes. Hematol Oncol Clin North Am. 2008;22(3):509–526. doi:10.1016/j.hoc.2008.03.004

    Article  PubMed  Google Scholar 

  19. Anderson MS, Venanzi ES, Klein L, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298(5597):1395–1401. doi:10.1126/science.1075958

    Article  PubMed  CAS  Google Scholar 

  20. Ramsey C, Bukrinsky A, Peltonen L. Systematic mutagenesis of the functional domains of AIRE reveals their role in intracellular targeting. Hum Mol Genet. 2002;11(26):3299–3308. doi:10.1093/hmg/11.26.3299

    Article  PubMed  CAS  Google Scholar 

  21. Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC. Aire regulates negative selection of organ-specific T cells. Nat Immunol. 2003;4(4):350–354. doi:10.1038/ni906

    Article  PubMed  CAS  Google Scholar 

  22. Ramsey C, Winqvist O, Puhakka L, et al. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet. 2002;11(4):397–409. doi:10.1093/hmg/11.4.397

    Article  PubMed  CAS  Google Scholar 

  23. Strobel P, Murumagi A, Klein R, et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). J Pathol. 2007;211(5):563–571. doi:10.1002/path.2141

    Article  PubMed  CAS  Google Scholar 

  24. Meloni A, Furcas M, Cetani F, et al.: Autoantibodies against type I Interferons as an additional diagnostic criteria for Autoimmune Polyendocrine Syndrome Type I. J Clin Endocrinol Metab Aug 26 2008

  25. Suzuki E, Kobayashi Y, Yano M, Fujii Y. Infrequent and low AIRE expression in thymoma: difference in AIRE expression among WHO subtypes does not correlate with association of MG. Autoimmunity. 2008;41(5):377–382. doi:10.1080/08916930801987573

    Article  PubMed  CAS  Google Scholar 

  26. Okumura M, Fujii Y, Shiono H, et al. Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis. Gen Thorac Cardiovasc Surg. 2008;56(4):143–150. doi:10.1007/s11748-007-0185-8

    Article  PubMed  Google Scholar 

  27. Evoli A, Minicuci GM, Vitaliani R, et al. Paraneoplastic diseases associated with thymoma. J Neurol. 2007;254(6):756–762. doi:10.1007/s00415-006-0429-z

    Article  PubMed  Google Scholar 

  28. Scarpino S, Di Napoli A, Stoppacciaro A, et al. Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas. Clin Exp Immunol. 2007;149(3):504–512.

    PubMed  CAS  Google Scholar 

  29. Zamecnik J, Vesely D, Jakubicka B, et al. Muscle lymphocytic infiltrates in thymoma-associated myasthenia gravis are phenotypically different from those in polymyositis. Neuromuscul Disord. 2007;17(11–12):935–942. doi:10.1016/j.nmd.2007.05.010

    Article  PubMed  Google Scholar 

  30. Alexiev BA, Drachenberg CB, Burke AP. Thymomas: a cytological and immunohistochemical study, with emphasis on lymphoid and neuroendocrine markers. Diagn Pathol. 2007;2:13. doi:10.1186/1746-1596-2-13

    Article  PubMed  Google Scholar 

  31. Storstein A, Vedeler CA. Paraneoplastic neurological syndromes and onconeural antibodies: clinical and immunological aspects. Adv Clin Chem. 2007;44:143–185. doi:10.1016/S0065-2423(07)44005-7

    Article  PubMed  CAS  Google Scholar 

  32. Zhu X, Zhang B. Paraneoplastic pemphigus. J Dermatol. 2007;34(8):503–511. doi:10.1111/j.1346-8138.2007.00322.x

    Article  PubMed  CAS  Google Scholar 

  33. Barbetakis N, Samanidis G, Paliouras D, et al. 2008 Paraneoplastic pemphigus regression after thymoma resection. World J Surg Oncol. 6:83. doi:10.1186/1477-7819-6-83

    Article  PubMed  Google Scholar 

  34. Malhotra P, Muralikrishna GK, Varma N, et al. Spectrum of pure red cell aplasia in adult population of north-west India. Hematology. 2008;13(2):88–91. doi:10.1179/102453308X315979

    Article  PubMed  Google Scholar 

  35. Wadhera A, Maverakis E, Mitsiades N, Lara PN, Fung MA, Lynch PJ. Thymoma-associated multiorgan autoimmunity: a graft-versus-host-like disease. J Am Acad Dermatol. 2007;57(4):683–689. doi:10.1016/j.jaad.2007.02.027

    Article  PubMed  Google Scholar 

  36. Offerhaus GJ, Schipper ME, Lazenby AJ, et al. Graft-versus-host-like disease complicating thymoma: lack of AIRE expression as a cause of non-hereditary autoimmunity? Immunol Lett. 2007;114(1):31–37. doi:10.1016/j.imlet.2007.08.010

    Article  PubMed  CAS  Google Scholar 

  37. Arcasoy MO, Gockerman JP. Aplastic anaemia as an autoimmune complication of thymoma. Br J Haematol. 2007;137(4):272. doi:10.1111/j.1365-2141.2007.06523.x

    Article  PubMed  Google Scholar 

  38. Wong IW, Chan KK, Chan KS. Good’s syndrome. Hong Kong Med J. 2008;14(3):246.

    PubMed  Google Scholar 

  39. Yong DS, Tsang MK, Chan EY, Tse DM. Good’s syndrome in a patient with cytomegalovirus retinitis. Hong Kong Med J. 2008;14(2):142–144.

    PubMed  Google Scholar 

  40. Seneschal J, Orlandini V, Duffau P, et al. Oral erosive lichen planus and Good’s syndrome: just a coincidence or a direct link between the two diseases? J Eur Acad Dermatol Venereol. 2008;22(4):506–507. doi:10.1111/j.1468-3083.2007.02370.x

    Article  PubMed  CAS  Google Scholar 

  41. Khicha SG, Kaiser LR, Shrager JB. Extended transcervical thymectomy in the treatment of myasthenia gravis. Ann N Y Acad Sci. 2008;1132:336–343. doi:10.1196/annals.1405.006

    Article  PubMed  Google Scholar 

  42. Zisimopoulou P, Lagoumintzis G, Kostelidou K, et al. Towards antigen-specific apheresis of pathogenic autoantibodies as a further step in the treatment of myasthenia gravis by plasmapheresis. J Neuroimmunol. 2008;201–202:95–103. doi:10.1016/j.jneuroim.2008.06.020

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN, USA

    Robert P. Nelson Jr. MD

  2. Department of Neurology, 545, Barnhill Drive EH 125, Indianapolis, IN, 46202-5124, USA

    Robert M. Pascuzzi MD

Authors
  1. Robert P. Nelson Jr. MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert M. Pascuzzi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert P. Nelson Jr. MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nelson, R.P., Pascuzzi, R.M. Paraneoplastic Syndromes in Thymoma: An Immunological Perspective. Curr. Treat. Options in Oncol. 9, 269–276 (2008). https://doi.org/10.1007/s11864-008-0081-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-008-0081-1

Search

Navigation